                         б

<110>  պҽҩɷ޹˾Ϻҽҩ޹˾
 
<120>  һPCSK-9ҩＰ;

<130>  P184015150C

<150>  CN201710519829.6
<151>  2017-06-30

<160>  33    

<170>  PatentIn version 3.5

<210>  1
<211>  698
<212>  PRT
<213>  ˹

<220>
<223>  HisǩpCSK9pCSK9-His6ԭСԼ

<400>  1

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


Asp Ala Cys Leu Tyr Ser Pro Ala Ser Ala Pro Glu Val Ile Thr Val 
                325                 330                 335     


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Asp Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Gly Ala Gly Trp Gln Leu Phe Cys Arg Thr Val Trp Ser Ala His 
    450                 455                 460                 


Ser Gly Pro Thr Arg Met Ala Thr Ala Val Ala Arg Cys Ala Pro Asp 
465                 470                 475                 480 


Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser Arg Ser Gly Lys Arg Arg 
                485                 490                 495     


Gly Glu Arg Met Glu Ala Gln Gly Gly Lys Leu Val Cys Arg Ala His 
            500                 505                 510         


Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala Ile Ala Arg Cys Cys Leu 
        515                 520                 525             


Leu Pro Gln Ala Asn Cys Ser Val His Thr Ala Pro Pro Ala Glu Ala 
    530                 535                 540                 


Ser Met Gly Thr Arg Val His Cys His Gln Gln Gly His Val Leu Thr 
545                 550                 555                 560 


Gly Cys Ser Ser His Trp Glu Val Glu Asp Leu Gly Thr His Lys Pro 
                565                 570                 575     


Pro Val Leu Arg Pro Arg Gly Gln Pro Asn Gln Cys Val Gly His Arg 
            580                 585                 590         


Glu Ala Ser Ile His Ala Ser Cys Cys His Ala Pro Gly Leu Glu Cys 
        595                 600                 605             


Lys Val Lys Glu His Gly Ile Pro Ala Pro Gln Glu Gln Val Thr Val 
    610                 615                 620                 


Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly Cys Ser Ala Leu Pro Gly 
625                 630                 635                 640 


Thr Ser His Val Leu Gly Ala Tyr Ala Val Asp Asn Thr Cys Val Val 
                645                 650                 655     


Arg Ser Arg Asp Val Ser Thr Thr Gly Ser Thr Ser Glu Gly Ala Val 
            660                 665                 670         


Thr Ala Val Ala Ile Cys Cys Arg Ser Arg His Leu Ala Gln Ala Ser 
        675                 680                 685             


Gln Glu Leu Gln His His His His His His 
    690                 695             


<210>  2
<211>  714
<212>  PRT
<213>  ˹

<220>
<223>  PADREĺHisǩpCSK9pCSK9-PADRE-His6ΪԭPADR
       EĿԴٽ

<400>  2

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


Asp Ala Cys Leu Tyr Ser Pro Ala Ser Ala Pro Glu Val Ile Thr Val 
                325                 330                 335     


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Asp Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Gly Ala Gly Trp Gln Leu Phe Cys Arg Thr Val Trp Ser Ala His 
    450                 455                 460                 


Ser Gly Pro Thr Arg Met Ala Thr Ala Val Ala Arg Cys Ala Pro Asp 
465                 470                 475                 480 


Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser Arg Ser Gly Lys Arg Arg 
                485                 490                 495     


Gly Glu Arg Met Glu Ala Gln Gly Gly Lys Leu Val Cys Arg Ala His 
            500                 505                 510         


Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala Ile Ala Arg Cys Cys Leu 
        515                 520                 525             


Leu Pro Gln Ala Asn Cys Ser Val His Thr Ala Pro Pro Ala Glu Ala 
    530                 535                 540                 


Ser Met Gly Thr Arg Val His Cys His Gln Gln Gly His Val Leu Thr 
545                 550                 555                 560 


Gly Cys Ser Ser His Trp Glu Val Glu Asp Leu Gly Thr His Lys Pro 
                565                 570                 575     


Pro Val Leu Arg Pro Arg Gly Gln Pro Asn Gln Cys Val Gly His Arg 
            580                 585                 590         


Glu Ala Ser Ile His Ala Ser Cys Cys His Ala Pro Gly Leu Glu Cys 
        595                 600                 605             


Lys Val Lys Glu His Gly Ile Pro Ala Pro Gln Glu Gln Val Thr Val 
    610                 615                 620                 


Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly Cys Ser Ala Leu Pro Gly 
625                 630                 635                 640 


Thr Ser His Val Leu Gly Ala Tyr Ala Val Asp Asn Thr Cys Val Val 
                645                 650                 655     


Arg Ser Arg Asp Val Ser Thr Thr Gly Ser Thr Ser Glu Gly Ala Val 
            660                 665                 670         


Thr Ala Val Ala Ile Cys Cys Arg Ser Arg His Leu Ala Gln Ala Ser 
        675                 680                 685             


Gln Glu Leu Gln Gly Ser Gly Ala Lys Phe Val Ala Ala Trp Thr Leu 
    690                 695                 700                 


Lys Ala Ala Ala His His His His His His 
705                 710                 


<210>  3
<211>  704
<212>  PRT
<213>  ˹

<220>
<223>  TEVøλ 
       pCSK9hisǩںϵףpCSK9-TEV-His6ͨTEVøлN-pCSK9
       NpCSK9ṹ򣩣Ϊԭ

<400>  3

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


Asp Ala Cys Leu Tyr Ser Pro Ala Ser Ala Pro Glu Val Ile Thr Val 
                325                 330                 335     


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Asp Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Glu Asn Leu Tyr Phe Gln Gly Ala Gly Trp Gln Leu Phe Cys Arg 
    450                 455                 460                 


Thr Val Trp Ser Ala His Ser Gly Pro Thr Arg Met Ala Thr Ala Val 
465                 470                 475                 480 


Ala Arg Cys Ala Pro Asp Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser 
                485                 490                 495     


Arg Ser Gly Lys Arg Arg Gly Glu Arg Met Glu Ala Gln Gly Gly Lys 
            500                 505                 510         


Leu Val Cys Arg Ala His Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala 
        515                 520                 525             


Ile Ala Arg Cys Cys Leu Leu Pro Gln Ala Asn Cys Ser Val His Thr 
    530                 535                 540                 


Ala Pro Pro Ala Glu Ala Ser Met Gly Thr Arg Val His Cys His Gln 
545                 550                 555                 560 


Gln Gly His Val Leu Thr Gly Cys Ser Ser His Trp Glu Val Glu Asp 
                565                 570                 575     


Leu Gly Thr His Lys Pro Pro Val Leu Arg Pro Arg Gly Gln Pro Asn 
            580                 585                 590         


Gln Cys Val Gly His Arg Glu Ala Ser Ile His Ala Ser Cys Cys His 
        595                 600                 605             


Ala Pro Gly Leu Glu Cys Lys Val Lys Glu His Gly Ile Pro Ala Pro 
    610                 615                 620                 


Gln Glu Gln Val Thr Val Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly 
625                 630                 635                 640 


Cys Ser Ala Leu Pro Gly Thr Ser His Val Leu Gly Ala Tyr Ala Val 
                645                 650                 655     


Asp Asn Thr Cys Val Val Arg Ser Arg Asp Val Ser Thr Thr Gly Ser 
            660                 665                 670         


Thr Ser Glu Gly Ala Val Thr Ala Val Ala Ile Cys Cys Arg Ser Arg 
        675                 680                 685             


His Leu Ala Gln Ala Ser Gln Glu Leu Gln His His His His His His 
    690                 695                 700                 


<210>  4
<211>  698
<212>  PRT
<213>  ˹

<220>
<223>  pCSK9-D374Yͻ䵰ףhisǩpCSK9-D374Y-His6ΪԼ

<400>  4

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


Asp Ala Cys Leu Tyr Ser Pro Ala Ser Ala Pro Glu Val Ile Thr Val 
                325                 330                 335     


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Tyr Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Gly Ala Gly Trp Gln Leu Phe Cys Arg Thr Val Trp Ser Ala His 
    450                 455                 460                 


Ser Gly Pro Thr Arg Met Ala Thr Ala Val Ala Arg Cys Ala Pro Asp 
465                 470                 475                 480 


Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser Arg Ser Gly Lys Arg Arg 
                485                 490                 495     


Gly Glu Arg Met Glu Ala Gln Gly Gly Lys Leu Val Cys Arg Ala His 
            500                 505                 510         


Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala Ile Ala Arg Cys Cys Leu 
        515                 520                 525             


Leu Pro Gln Ala Asn Cys Ser Val His Thr Ala Pro Pro Ala Glu Ala 
    530                 535                 540                 


Ser Met Gly Thr Arg Val His Cys His Gln Gln Gly His Val Leu Thr 
545                 550                 555                 560 


Gly Cys Ser Ser His Trp Glu Val Glu Asp Leu Gly Thr His Lys Pro 
                565                 570                 575     


Pro Val Leu Arg Pro Arg Gly Gln Pro Asn Gln Cys Val Gly His Arg 
            580                 585                 590         


Glu Ala Ser Ile His Ala Ser Cys Cys His Ala Pro Gly Leu Glu Cys 
        595                 600                 605             


Lys Val Lys Glu His Gly Ile Pro Ala Pro Gln Glu Gln Val Thr Val 
    610                 615                 620                 


Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly Cys Ser Ala Leu Pro Gly 
625                 630                 635                 640 


Thr Ser His Val Leu Gly Ala Tyr Ala Val Asp Asn Thr Cys Val Val 
                645                 650                 655     


Arg Ser Arg Asp Val Ser Thr Thr Gly Ser Thr Ser Glu Gly Ala Val 
            660                 665                 670         


Thr Ala Val Ala Ile Cys Cys Arg Ser Arg His Leu Ala Gln Ala Ser 
        675                 680                 685             


Gln Glu Leu Gln His His His His His His 
    690                 695             


<210>  5
<211>  719
<212>  PRT
<213>  ˹

<220>
<223>  ؽļhisǩpCSK9ףpCSK9-BP15-His6Ϊ
       BP15λڱܹرǣرǼ
       ܵµĹ仯

<400>  5

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


Asp Ala Cys Leu Tyr Ser Pro Ala Ser Ala Pro Glu Val Ile Thr Val 
                325                 330                 335     


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Asp Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Gly Ala Gly Trp Gln Leu Phe Cys Arg Thr Val Trp Ser Ala His 
    450                 455                 460                 


Ser Gly Pro Thr Arg Met Ala Thr Ala Val Ala Arg Cys Ala Pro Asp 
465                 470                 475                 480 


Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser Arg Ser Gly Lys Arg Arg 
                485                 490                 495     


Gly Glu Arg Met Glu Ala Gln Gly Gly Lys Leu Val Cys Arg Ala His 
            500                 505                 510         


Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala Ile Ala Arg Cys Cys Leu 
        515                 520                 525             


Leu Pro Gln Ala Asn Cys Ser Val His Thr Ala Pro Pro Ala Glu Ala 
    530                 535                 540                 


Ser Met Gly Thr Arg Val His Cys His Gln Gln Gly His Val Leu Thr 
545                 550                 555                 560 


Gly Cys Ser Ser His Trp Glu Val Glu Asp Leu Gly Thr His Lys Pro 
                565                 570                 575     


Pro Val Leu Arg Pro Arg Gly Gln Pro Asn Gln Cys Val Gly His Arg 
            580                 585                 590         


Glu Ala Ser Ile His Ala Ser Cys Cys His Ala Pro Gly Leu Glu Cys 
        595                 600                 605             


Lys Val Lys Glu His Gly Ile Pro Ala Pro Gln Glu Gln Val Thr Val 
    610                 615                 620                 


Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly Cys Ser Ala Leu Pro Gly 
625                 630                 635                 640 


Thr Ser His Val Leu Gly Ala Tyr Ala Val Asp Asn Thr Cys Val Val 
                645                 650                 655     


Arg Ser Arg Asp Val Ser Thr Thr Gly Ser Thr Ser Glu Gly Ala Val 
            660                 665                 670         


Thr Ala Val Ala Ile Cys Cys Arg Ser Arg His Leu Ala Gln Ala Ser 
        675                 680                 685             


Gln Glu Leu Gln Gly Ser Thr Ser Gly Ser Gly Leu Asn Asp Ile Phe 
    690                 695                 700                 


Glu Ala Gln Lys Ile Glu Trp His Glu His His His His His His 
705                 710                 715                 


<210>  6
<211>  719
<212>  PRT
<213>  ˹

<220>
<223>  ؽļhisǩpCSK9 
       D374Yͻ嵰ףpCSK9-D374Y-BP15-His6⵰

<400>  6

Met Gly Thr Val Ser Ser Arg Arg Ser Trp Trp Pro Leu Pro Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Pro Ala Gly Ala Arg Ala Gln Glu 
            20                  25                  30          


Asp Glu Asp Gly Asp Tyr Glu Glu Leu Val Leu Ala Leu Arg Ser Glu 
        35                  40                  45              


Glu Asp Gly Leu Ala Glu Ala Pro Glu His Gly Thr Thr Ala Thr Phe 
    50                  55                  60                  


His Arg Cys Ala Lys Asp Pro Trp Arg Leu Pro Gly Thr Tyr Val Val 
65                  70                  75                  80  


Val Leu Lys Glu Glu Thr His Leu Ser Gln Ser Glu Arg Thr Ala Arg 
                85                  90                  95      


Arg Leu Gln Ala Gln Ala Ala Arg Arg Gly Tyr Leu Thr Lys Ile Leu 
            100                 105                 110         


His Val Phe His Gly Leu Leu Pro Gly Phe Leu Val Lys Met Ser Gly 
        115                 120                 125             


Asp Leu Leu Glu Leu Ala Leu Lys Leu Pro His Val Asp Tyr Ile Glu 
    130                 135                 140                 


Glu Asp Ser Ser Val Phe Ala Gln Ser Ile Pro Trp Asn Leu Glu Arg 
145                 150                 155                 160 


Ile Thr Pro Pro Arg Tyr Arg Ala Asp Glu Tyr Gln Pro Pro Asp Gly 
                165                 170                 175     


Gly Ser Leu Val Glu Val Tyr Leu Leu Asp Thr Ser Ile Gln Ser Asp 
            180                 185                 190         


His Arg Glu Ile Glu Gly Arg Val Met Val Thr Asp Phe Glu Asn Val 
        195                 200                 205             


Pro Glu Glu Asp Gly Thr Arg Phe His Arg Gln Ala Ser Lys Cys Asp 
    210                 215                 220                 


Ser His Gly Thr His Leu Ala Gly Val Val Ser Gly Arg Asp Ala Gly 
225                 230                 235                 240 


Val Ala Lys Gly Ala Ser Met Arg Ser Leu Arg Val Leu Asn Cys Gln 
                245                 250                 255     


Gly Lys Gly Thr Val Ser Gly Thr Leu Ile Gly Leu Glu Phe Ile Arg 
            260                 265                 270         


Lys Ser Gln Leu Val Gln Pro Val Gly Pro Leu Val Val Leu Leu Pro 
        275                 280                 285             


Leu Ala Gly Gly Tyr Ser Arg Val Leu Asn Ala Ala Cys Gln Arg Leu 
    290                 295                 300                 


Ala Arg Ala Gly Val Val Leu Val Thr Ala Ala Gly Asn Phe Arg Asp 
305                 310                 315                 320 


Asp Ala Cys Leu Tyr Ser Pro Ala Ser Ala Pro Glu Val Ile Thr Val 
                325                 330                 335     


Gly Ala Thr Asn Ala Gln Asp Gln Pro Val Thr Leu Gly Thr Leu Gly 
            340                 345                 350         


Thr Asn Phe Gly Arg Cys Val Asp Leu Phe Ala Pro Gly Glu Asp Ile 
        355                 360                 365             


Ile Gly Ala Ser Ser Tyr Cys Ser Thr Cys Phe Val Ser Gln Ser Gly 
    370                 375                 380                 


Thr Ser Gln Ala Ala Ala His Val Ala Gly Ile Ala Ala Met Met Leu 
385                 390                 395                 400 


Ser Ala Glu Pro Glu Leu Thr Leu Ala Glu Leu Arg Gln Arg Leu Ile 
                405                 410                 415     


His Phe Ser Ala Lys Asp Val Ile Asn Glu Ala Trp Phe Pro Glu Asp 
            420                 425                 430         


Gln Arg Val Leu Thr Pro Asn Leu Val Ala Ala Leu Pro Pro Ser Thr 
        435                 440                 445             


His Gly Ala Gly Trp Gln Leu Phe Cys Arg Thr Val Trp Ser Ala His 
    450                 455                 460                 


Ser Gly Pro Thr Arg Met Ala Thr Ala Val Ala Arg Cys Ala Pro Asp 
465                 470                 475                 480 


Glu Glu Leu Leu Ser Cys Ser Ser Phe Ser Arg Ser Gly Lys Arg Arg 
                485                 490                 495     


Gly Glu Arg Met Glu Ala Gln Gly Gly Lys Leu Val Cys Arg Ala His 
            500                 505                 510         


Asn Ala Phe Gly Gly Glu Gly Val Tyr Ala Ile Ala Arg Cys Cys Leu 
        515                 520                 525             


Leu Pro Gln Ala Asn Cys Ser Val His Thr Ala Pro Pro Ala Glu Ala 
    530                 535                 540                 


Ser Met Gly Thr Arg Val His Cys His Gln Gln Gly His Val Leu Thr 
545                 550                 555                 560 


Gly Cys Ser Ser His Trp Glu Val Glu Asp Leu Gly Thr His Lys Pro 
                565                 570                 575     


Pro Val Leu Arg Pro Arg Gly Gln Pro Asn Gln Cys Val Gly His Arg 
            580                 585                 590         


Glu Ala Ser Ile His Ala Ser Cys Cys His Ala Pro Gly Leu Glu Cys 
        595                 600                 605             


Lys Val Lys Glu His Gly Ile Pro Ala Pro Gln Glu Gln Val Thr Val 
    610                 615                 620                 


Ala Cys Glu Glu Gly Trp Thr Leu Thr Gly Cys Ser Ala Leu Pro Gly 
625                 630                 635                 640 


Thr Ser His Val Leu Gly Ala Tyr Ala Val Asp Asn Thr Cys Val Val 
                645                 650                 655     


Arg Ser Arg Asp Val Ser Thr Thr Gly Ser Thr Ser Glu Gly Ala Val 
            660                 665                 670         


Thr Ala Val Ala Ile Cys Cys Arg Ser Arg His Leu Ala Gln Ala Ser 
        675                 680                 685             


Gln Glu Leu Gln Gly Ser Thr Ser Gly Ser Gly Leu Asn Asp Ile Phe 
    690                 695                 700                 


Glu Ala Gln Lys Ile Glu Trp His Glu His His His His His His 
705                 710                 715                 


<210>  7
<211>  802
<212>  PRT
<213>  ˹

<220>
<223>  FlagǩHisǩpCSK9嵰LDLRƬΣLDLR-ECD-Flag-H
       is6Լ

<400>  7

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


Tyr Asp Thr Val Ile Ser Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala 
465                 470                 475                 480 


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


His Gln Ala Leu Gly Asp Val Ala Gly Arg Gly Asn Glu Lys Lys Pro 
    770                 775                 780                 


Ser Ser Val Arg Asp Tyr Lys Asp Asp Asp Asp Lys His His His His 
785                 790                 795                 800 


His His 
        


<210>  8
<211>  331
<212>  PRT
<213>  ˹

<220>
<223>  ʽLDLRƬhIgG1-FcںϵףpCSK9ϻԣ
       LDLR-sECD -FchIgG1ΪԼ

<400>  8

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly Cys Ser 
            20                  25                  30          


His Val Cys Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys Pro Asp 
        35                  40                  45              


Gly Phe Gln Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp Glu Cys 
    50                  55                  60                  


Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys Val Asn Leu Glu Gly Gly 
65                  70                  75                  80  


Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln Leu Asp Pro His Thr Lys 
                85                  90                  95      


Ala Cys Lys Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro 
            100                 105                 110         


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
        115                 120                 125             


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
    130                 135                 140                 


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
145                 150                 155                 160 


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
                165                 170                 175     


Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
            180                 185                 190         


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
        195                 200                 205             


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
    210                 215                 220                 


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
225                 230                 235                 240 


Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
                245                 250                 255     


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
            260                 265                 270         


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
        275                 280                 285             


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
    290                 295                 300                 


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
305                 310                 315                 320 


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330     


<210>  9
<211>  294
<212>  PRT
<213>  ˹

<220>
<223>  ʽLDLRƬhIgG1-FcںϵףpCSK9ϻ
       ԣLDLR-ssECD -FchIgG1ΪԼ

<400>  9

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys Gly Thr Asn Glu Cys Leu Asp Asn Asn Gly Gly Cys Ser 
            20                  25                  30          


His Val Cys Asn Asp Leu Lys Ile Gly Tyr Glu Cys Leu Cys Pro Asp 
        35                  40                  45              


Gly Phe Gln Leu Val Ala Gln Arg Arg Cys Glu Asp Ile Asp Glu Pro 
    50                  55                  60                  


Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
65                  70                  75                  80  


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                85                  90                  95      


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            100                 105                 110         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        115                 120                 125             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    130                 135                 140                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
145                 150                 155                 160 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                165                 170                 175     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            180                 185                 190         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        195                 200                 205             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    210                 215                 220                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
225                 230                 235                 240 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                245                 250                 255     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            260                 265                 270         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        275                 280                 285             


Ser Leu Ser Pro Gly Lys 
    290                 


<210>  10
<211>  121
<212>  PRT
<213> 

<400>  10

Gln Val His Leu Gln Gln Ser Gly Ala Glu Leu Ala Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Asn Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Lys Glu Arg Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Gln Leu Ser Ser Leu Thr Tyr Asp Asp Ser Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Thr Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  11
<211>  112
<212>  PRT
<213> 

<400>  11

Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly 
1               5                   10                  15      


Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Arg Thr Arg Lys Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Thr Gly Arg Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Lys Gln 
                85                  90                  95      


Ser Phe Asn Leu Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  12
<211>  5
<212>  PRT
<213> 

<400>  12

Asp Tyr Trp Met His 
1               5   


<210>  13
<211>  17
<212>  PRT
<213> 

<400>  13

Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  14
<211>  12
<212>  PRT
<213> 

<400>  14

Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val 
1               5                   10          


<210>  15
<211>  17
<212>  PRT
<213> 

<400>  15

Lys Ser Ser Gln Ser Leu Leu Asn Ser Arg Thr Arg Lys Asn Phe Leu 
1               5                   10                  15      


Ala 
    


<210>  16
<211>  7
<212>  PRT
<213> 

<400>  16

Trp Ala Ser Thr Arg Glu Ser 
1               5           


<210>  17
<211>  8
<212>  PRT
<213> 

<400>  17

Lys Gln Ser Phe Asn Leu Phe Thr 
1               5               


<210>  18
<211>  121
<212>  PRT
<213>  ˹

<220>
<223>  ch-001

<400>  18

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  19
<211>  121
<212>  PRT
<213>  ˹

<220>
<223>  h001-VH.1A

<400>  19

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Asn Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  20
<211>  121
<212>  PRT
<213>  ˹

<220>
<223>  h001-VH.1B

<400>  20

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Thr Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  21
<211>  121
<212>  PRT
<213>  ˹

<220>
<223>  h001-VH.1C

<400>  21

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Asn Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Thr Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  22
<211>  121
<212>  PRT
<213>  ˹

<220>
<223>  h001-VH.1D

<400>  22

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Asn Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Thr Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  23
<211>  121
<212>  PRT
<213>  ˹

<220>
<223>  h001-VH.1E

<400>  23

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Asn Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Lys Ala Thr Leu Thr Ala Asp Lys Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Thr Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  24
<211>  112
<212>  PRT
<213>  ˹

<220>
<223>  ch-001 hVL.1 (CDR֦)

<400>  24

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Arg Thr Arg Lys Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
        35                  40                  45              


Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Lys Gln 
                85                  90                  95      


Ser Phe Asn Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  25
<211>  112
<212>  PRT
<213>  ˹

<220>
<223>  h001-VL.1A

<400>  25

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Arg Thr Arg Lys Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
        35                  40                  45              


Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Lys Gln 
                85                  90                  95      


Ser Phe Asn Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  26
<211>  112
<212>  PRT
<213>  ˹

<220>
<223>  h001-VL.1B

<400>  26

Asp Ile Gln Met Ser Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Arg Thr Arg Lys Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
        35                  40                  45              


Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Lys Gln 
                85                  90                  95      


Ser Phe Asn Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  27
<211>  112
<212>  PRT
<213>  ˹

<220>
<223>  h001-VL.1C

<400>  27

Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Arg Thr Arg Lys Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
        35                  40                  45              


Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Lys Gln 
                85                  90                  95      


Ser Phe Asn Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  28
<211>  451
<212>  PRT
<213>  ˹

<220>
<223> h001-4-IgG1

<400>  28

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
    130                 135                 140                 


Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
145                 150                 155                 160 


Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
        195                 200                 205             


Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 
    210                 215                 220                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                245                 250                 255     


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            260                 265                 270         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        275                 280                 285             


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
    290                 295                 300                 


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
305                 310                 315                 320 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                325                 330                 335     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            340                 345                 350         


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
        355                 360                 365             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    370                 375                 380                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
385                 390                 395                 400 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            420                 425                 430         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        435                 440                 445             


Pro Gly Lys 
    450     


<210>  29
<211>  1413
<212>  DNA
<213>  ˹

<220>
<223>  h001-4-IgG1

<400>  29
atggagtttg ggctgagctg gctttttctt gtcgcgattc ttaagggtgt ccagtgccag       60

gtgcagctgg tgcagagcgg cgctgaggtg aagaagcccg gagcgagcgt aaaggtgagc      120

tgcaaggcca gcggatacac cttcaccgac tactggatgc actgggtgag gcaggcccca      180

ggacagggcc tggagtggat gggctacatc aaccccagca gcggctttac caagtatcac      240

cagaacttca aagacagggt gaccatgacc agggacacca gcatcagcac cgcctacatg      300

gagctgagca ggctgaggag cgacgacacc gccgtgtact actgcgccag gcaatacgac      360

tacgacgagg actggtactt cgacgtgtgg ggccaaggaa ccaccgtgac tgtgagcagc      420

gcttcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      480

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      540

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      660

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc      720

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      780

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      840

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      900

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac      960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag     1020

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1080

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     1140

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     1260

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1320

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1380

cagaagagcc tctccctgtc tccgggtaaa tga                                  1413


<210>  30
<211>  219
<212>  PRT
<213>  ˹

<220>
<223>  h001-4-kappa

<400>  30

Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Arg Thr Arg Lys Asn Phe Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
        35                  40                  45              


Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Lys Gln 
                85                  90                  95      


Ser Phe Asn Leu Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  31
<211>  726
<212>  DNA
<213>  ˹

<220>
<223>  h001-4-kappa

<400>  31
atggacatgc gcgtgcccgc ccagctgctg ggcctgctgc tgctgtggtt ccccggctcg       60

cgatgcgaca tcgtgatgtc tcagagccca tctagcctga gcgccagcgt gggcgacagg      120

gtaaccatca cctgcaagag cagccaaagc ctgctgaaca gcaggacccg caagaacttc      180

ctggcttggt atcagcagaa gcccggcaag tctcccaagt tgctgatcta ctgggccagc      240

accagggaga gcggcgtgcc cgacaggttc agcggctccg gcagcggcac cgacttcacc      300

ctgaccatct ctagtctgca gcccgaggac ttcgccacct actactgcaa gcagagcttc      360

aatctgttca ccttcggcca gggcaccaag ctggagatca agcgtacggt ggctgcacca      420

tctgtcttca tcttcccgcc atctgatgag cagttgaaat ctggaactgc ctctgttgtg      480

tgcctgctga ataacttcta tcccagagag gccaaagtac agtggaaggt ggataacgcc      540

ctccaatcgg gtaactccca ggagagtgtc acagagcagg acagcaagga cagcacctac      600

agcctcagca gcaccctgac gctgagcaaa gcagactacg agaaacacaa agtctacgcc      660

tgcgaagtca cccatcaggg cctgagctcg cccgtcacaa agagcttcaa caggggagag      720

tgttga                                                                 726


<210>  32
<211>  451
<212>  PRT
<213>  ˹

<220>
<223>  h001-4-IgG1-YTE

<400>  32

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Tyr Ile Asn Pro Ser Ser Gly Phe Thr Lys Tyr His Gln Asn Phe 
    50                  55                  60                  


Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gln Tyr Asp Tyr Asp Glu Asp Trp Tyr Phe Asp Val Trp Gly 
            100                 105                 110         


Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             


Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala 
    130                 135                 140                 


Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
145                 150                 155                 160 


Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     


Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         


Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His 
        195                 200                 205             


Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 
    210                 215                 220                 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
225                 230                 235                 240 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr 
                245                 250                 255     


Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
            260                 265                 270         


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
        275                 280                 285             


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
    290                 295                 300                 


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
305                 310                 315                 320 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                325                 330                 335     


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
            340                 345                 350         


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
        355                 360                 365             


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
    370                 375                 380                 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
385                 390                 395                 400 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                405                 410                 415     


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
            420                 425                 430         


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
        435                 440                 445             


Pro Gly Lys 
    450     


<210>  33
<211>  1413
<212>  DNA
<213>  ˹

<220>
<223>  h001-4-IgG1-YTE

<400>  33
atggagtttg ggctgagctg gctttttctt gtcgcgattc ttaagggtgt ccagtgccag       60

gtgcagctgg tgcagagcgg cgctgaggtg aagaagcccg gagcgagcgt aaaggtgagc      120

tgcaaggcca gcggatacac cttcaccgac tactggatgc actgggtgag gcaggcccca      180

ggacagggcc tggagtggat gggctacatc aaccccagca gcggctttac caagtatcac      240

cagaacttca aagacagggt gaccatgacc agggacacca gcatcagcac cgcctacatg      300

gagctgagca ggctgaggag cgacgacacc gccgtgtact actgcgccag gcaatacgac      360

tacgacgagg actggtactt cgacgtgtgg ggccaaggaa ccaccgtgac tgtgagcagc      420

gcttcgacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      480

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      540

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      660

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc      720

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      780

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tctacatcac ccgggagcct      840

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      900

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac      960

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag     1020

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1080

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     1140

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1200

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     1260

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1320

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1380

cagaagagcc tctccctgtc tccgggtaaa tga                                  1413



